Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts.

Cell shape is a powerful readout of cell state, fate and function. We describe a custom workflow to perform semi-automated, 3D cell and nucleus segmentation, and spherical harmonics and principal components analysis to distill cell and nuclear shape variation into discrete biologically meaningful parameters. We apply these methods to analyze shape in the neuromast cells of the zebrafish lateral line system, finding that shapes vary with cell location and identity. The distinction between hair cells and support cells accounted for much of the variation, which allowed us to train classifiers to predict cell identity from shape features. Using transgenic markers for support cell subpopulations, we found that subtypes had different shapes from each other. To investigate how loss of a neuromast cell type altered cell shape distributions, we examined atoh1a mutants that lack hair cells. We found that mutant neuromasts lacked the cell shape phenotype associated with hair cells, but did not exhibit a mutant-specific cell shape. Our results demonstrate the utility of using 3D cell shape features to characterize, compare and classify cells in a living developing organism.

Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance.

We have examined lateral line hair cell and support cell maintenance in adult zebrafish when growth is largely complete. We demonstrate that adult zebrafish not only replenish hair cells after a single instance of hair cell damage, but also maintain hair cells and support cells after multiple rounds of damage and regeneration. We find that hair cells undergo continuous turnover in adult zebrafish in the absence of damage. We identify mitotically-distinct support cell populations and show that hair cells regenerate from underlying support cells in a region-specific manner. Our results demonstrate that there are two distinct support cell populations in the lateral line, which may help explain why zebrafish hair cell regeneration is extremely robust, retained throughout life, and potentially unlimited in regenerative capacity.

Hypovitaminosis D and valvular calcification in patients with dilated cardiomyopathy.

BACKGROUND: In patients with dilated (idiopathic) cardiomyopathy (DCM), little is known about the presence of valvular calcification and its association with hypovitaminosis D, which may predispose affected tissues to calcification. Our objectives were 2-fold: to conduct a retrospective assessment of echocardiographic evidence of valvular calcification in patients with DCM who were known to have hypovitaminosis D (25(OH)D <30 ng/mL) and to conduct a prospective assessment of serum 25(OH)D in patients with DCM, who had demonstrated echocardiographic evidence of valvular calcification. METHODS: The retrospective study consisted of 48 African American patients (34 men, 14 women; 52.3 +/- 1.5 years) having DCM and ejection fraction <35% with serum creatinine <2.0 mg/dL and 25(OH)D <30 ng/mL; and 20 white patients in the prospective study (20 men; 71.0 +/- 3.0 years) having DCM and ejection fraction <35% with serum creatinine <2.0 mg/dL and echocardiographic evidence of valvular calcification. In the retrospective study, a transthoracic echocardiogram was obtained to address mitral valvular and annular calcification, aortic valvular calcification, and sinotubular calcification; whereas in the prospective study, serum 25(OH)D level was monitored in patients with known valvular calcification. Serum parathyroid hormone (PTH) was monitored in both studies. RESULTS: In the retrospective study, hypovitaminosis D was found in 19 patients (31%) with valvular calcification and in whom serum PTH was increased (83 +/- 8 pg/mL). In the prospective study, 15 of 20 elderly patients (80%) with known DCM and valvular calcification were found to have hypovitaminosis D (25(OH)D <30 ng/mL), whereas serum PTH was normal (43 +/- 4 pg/mL). CONCLUSIONS: In patients with DCM without marked renal dysfunction, valvular calcification was seen more frequently and associated with hypovitaminosis D, whereas in elderly patients with valvular calcification, hypovitaminosis D is common, suggesting that the duration of vitamin D deficiency may determine the extent of valvular calcification. The role of hypovitaminosis D in the appearance of valvular calcification deserves further study.

Functional valvular incompetence in decompensated heart failure: noninvasive monitoring and response to medical management.

OBJECTIVE: We hypothesized that functional mitral and tricuspid valvular incompetence (MR and TR, respectively) are reversible causes of reduced cardiac output in decompensated heart failure (DF) that accompanies systolic dysfunction in ischemic or nonischemic cardiomyopathy. BACKGROUND: DF, defined as signs and symptoms of heart failure at rest, is rooted in a salt-avid state transduced by neurohormonal activation secondary to impaired renal perfusion. Functional MR and TR are reversible causes of reduced systemic blood flow. Their impact on cardiac output, thoracic fluid content, cardiac chamber dimensions, and valvular apparatus function can be monitored noninvasively, before and after optimized medical management. METHODS: Fourteen male subjects (66 +/- 8 years old) with reduced ejection fraction (24 +/- 5%) secondary to ischemic (71%) or nonischemic (29%) cardiomyopathy, who developed DF with clinical evidence of mitral (MR) and tricuspid (TR) valvular incompetence, were each assessed by bioimpedance and echocardiography before and 1 week after optimized medical management restored compensated failure. RESULTS: Pharmacologic elimination of DF was accompanied by a reduction in body weight (P < 0.01). Hemodynamic improvements included a rise in cardiac index (2.1 to 2.6 L/min/m2; P < 0.01) and a reduction in predicted pulmonary artery systolic pressure (58 to 35 mm Hg; P < 0.001), thoracic fluid content (39 to 32 kOhm; P < 0.001), and systemic vascular resistance (1633 to 1209 dynes/sec/cm5; P < 0.001). Improvements in functional MR and TR included reductions in left and right atrial areas (27 to 24 cm and 26 to 23 cm2, respectively; P < 0.001), color-flow grading of MR and TR severity (P < 0.01), mitral regurgitant volume (105 to 65 mL; P < 0.001), and effective MR orifice size (0.8 to 0.6 cm2; P < 0.01). CONCLUSIONS: In DF, functional MR and TR contribute to reduced cardiac output, increased thoracic fluid content, and systemic vascular resistance, together with enlarged atria and valvular orifice size, which can be improved by medical management. Bioimpedance and echocardiography provide for serial noninvasive assessments of hemodynamic status and valvular function in such cases.

Echocardiography of the superior vena cava.

The anatomy and applied echocardiographic anatomy of the superior vena cava (SVC) are briefly described. Right supraclavicular interrogation of the SVC has been in use for many years, but supraclavicular two-dimensional (2-D) imaging of the SVC has been virtually ignored. We have recently shown that supraclavicular 2-D imaging can provide excellent views of the SVC and its main tributaries. Transthoracic echocardiography (TEE) is suitable for imaging of the lower (juxtaatrial) SVC. Persistence of a left SVC is an uncommon variant, diagnosed echocardiographically by coronary sinus dilatation and passage of contrast into it from a left arm vein. Extensive SVC compression by mediastinal masses is well known, but recently intravascular SVC obstruction has been increasingly reported as a complication of radiofrequency ablation for ectopic atrial tachycardia, for thrombosis of the SVC or its main tributaries following indwelling catheters, or following insertion of pacemaker leads. Doppler interrogation or TEE imaging of the SVC have been used in recent years to elucidate such pathology.

There and back again: development and regeneration of the zebrafish lateral line system.

The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprised of clusters of mechanosensory hair cells called neuromasts. The lateral line is initially established by a migratory group of cells, called a primordium, that deposits neuromasts at stereotyped locations along the surface of the fish. Wnt, FGF, and Notch signaling are all important regulators of various aspects of lateral line development, from primordium migration to hair cell specification. As zebrafish age, the organization of the lateral line becomes more complex in order to accommodate the fish's increased size. This expansion is regulated by many of the same factors involved in the initial development. Furthermore, unlike mammalian hair cells, lateral line hair cells have the capacity to regenerate after damage. New hair cells arise from the proliferation and differentiation of surrounding support cells, and the molecular and cellular pathways regulating this are beginning to be elucidated. All in all, the zebrafish lateral line has proven to be an excellent model in which to study a diverse array of processes, including collective cell migration, cell polarity, cell fate, and regeneration.

CHF: circulatory homeostasis gone awry.

The role of the renin-angiotensin-aldosterone system (RAAS) is integral to salt and water retention, particularly by the kidneys. Over time, positive sodium balance leads first to intra- and then to extravascular volume expansion, with subsequent symptomatic heart failure. This report examines the role of the RAAS in regulating a less well recognized component essential to circulatory homeostasis--central blood volume. The regulation of central blood volume draws on integrative cardiorenal physiology and a key role played by the RAAS in its regulation. In presenting insights into the role of the RAAS in regulating central blood volume, this review also addresses other sodium-retaining states with a predisposition to edema formation, such as cirrhosis and nephrosis.

Transthoracic Echocardiographic Visualization of Calcification of the Sinotubular Ridge of the Ascending Aorta.

Calcification of the ridge between the sinus of Valsalva and the tubular segments of the ascending aorta has been documented at autopsy, but no echocardiographic description has yet been published. We describe the two-dimensional echocardiographic appearances in 33 men (mean age, 69 years). Sinotubular ridge calcification manifested as a dense small echo projecting into the aortic lumen, precisely at the junction of the sinus of Valsalva and tubular aortic segments. Calcification in the aortic valve cusps, mitral annulus, basal mitral leaflets, and papillary muscles also were frequently present. This previously unknown entity must be distinguished from atheromatous aortic plaques.

Posterior Mediastinal Bronchogenic Cyst Compressing Left Atrium.

The echocardiographic literature contains exceedingly few reports of mediastinal bronchogenic cyst; in most published cases of this entity, the cysts were imaged by computed tomography or magnetic resonance imaging. Because mediastinal bronchogenic cyst is little known as a cause of cardiorespiratory symptoms, we report such a case.

Echocardiographic Features of Large Posterobasal Left Ventricular Aneurysms.

We describe the echocardiographic characteristics of 12 patients with left ventricular aneurysms involving posterobasal segments of the ventricular septum and of the adjacent ventricular wall. In 5, the septal as well as ventricular wall components of the aneurysm were both conspicuous; in 3 the septal but not ventricular wall component was large; and in 4 the ventricular wall part of the aneurysm was predominant. In all, the mouth (rim) of the aneurysm was wider than its fundus, thus distinguishing the posterobasal ventricular aneurysm from a pseudoaneurysm. The echographic features are striking, but are easily overlooked in standard echo planes. Aneurysmal complications (acquired ventricular septal defect, mural thrombus) can also be detected. Together with echo appearances, other consistent findings of this entity include deep, wide inferior Q waves, posteromedial papillary muscle calcification, and total or subtotal occlusion of right coronary or circumflex coronary artery. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

Echocardiography of the Inferior Vena Cava, Superior Vena Cava, and Coronary Sinus in Right Heart Failure.

Echocardiographic evaluation of the three major systemic venous channels that drain directly into the right atrium has hitherto received less attention than it deserves. Attention had been paid initially to inferior vena cava dilatation and lack of collapsibility (plethora) as signs of systemic venous congestion. Superior vena cava imaging has not been part of routine echographic evaluation; however, our recent observations on superior vena cava appearance by the right supraclavicular approach provide evidence that dilatation of superior vena cava correlates with that of inferior vena cava as a marker for venous congestion. The coronary sinus caliber, which has been virtually ignored, may also provide echographic signs of systemic congestion, namely, dilatation and lack of normal narrowing during atrial contraction.

Three-dimensional echocardiographic appearances of pericardial effusion with tamponade.

A patient with pericardial effusion and tamponade was studied by routine two-dimensional as well as three-dimensional echocardiogram. Chamber "collapses" of the right atrium, left atrium, right ventricle, and inferior vena cava were visualized by both modalities, but were better appreciated on three-dimensional echo imaging, perhaps because three-dimensional echo imaging is more suited to depicting three-dimensional changes in chamber shape.